Anti-inflammatory and immunomodulatory activities of stevioside and its metabolite steviol on THP-1 cells

Stevioside, a natural noncaloric sweetener isolated from Stevia rebaudiana Bertoni, possesses anti-inflammatory and antitumor promoting properties; however, no information is available to explain its activity. The aim of this study was to elucidate the anti-inflammatory and immunomodulatory activities of stevioside and its metabolite, steviol. Stevioside at 1 mM significantly suppressed lipopolysaccharide (LPS)-induced release of TNF-alpha and IL-1 beta and slightly suppressed nitric oxide release in THP-1 cells without exerting any direct toxic effect, whereas steviol at 100 mu M did not. Activation of IKK beta and transcription factor NF-kappa B were suppressed by stevioside, as demonstrated by Western blotting. Furthermore, only stevioside induced TNF-alpha, IL-1 beta, and nitric oxide release in unstimulated THP-1 cells. Release of TNF-alpha could be partially neutralized by anti-TLR4 antibody. This study suggested that stevioside attenuates synthesis of inflammatory mediators in LPS-stimulated THP-1 cells by interfering with the IKK beta and NF-kappa B signaling pathway, and stevioside-induced TNF-alpha secretion is partially mediated through TLR4.